Fig. 3.

Regulation of clathrin-mediated endocytosis (CME) by PICALM. (A) In a healthy brain, PICALM interacts with adaptor protein (AP) and clathrin at the plasma membrane. PICALM participates in CME and facilitates the formation of clathrin-coated vesicles (CCVs). This provides Aβ clearance. (B) PICALM and clathrin depletion in AD brain limited or stopped Aβ clearance. This increases the distribution of Aβ, intensifying neurotoxicity to neurons. In AD, abnormally cleaved PICALM was also associated with neurofibrillary tangles, co-localizing with conformationally abnormal and hyper-phosphorylated tau (P-tau) which contributes to endocytic dysfunction in AD